T cell homeostasis, gd T cells, CD8 T cells, Role of basophils in adaptive immunity
T cell homeostasis and lymphocyte dynamics
Biology of basophils and their roles in innate/adaptive immunity
Homeostatic regulation of T lymphocytes is a central mechanism by which the
immune system ensures its diversity and functionality. T cell deficiency triggers
a proliferative response of T cells that remain within such conditions or
that are adoptively transferred into such environments (which is often referred
to as homeostatic proliferation or endogenous proliferation). The proliferation
is often associated with a differentiation process that generates memory T
cells. The resulting memory T cells are thought to play a critical role in
the regulation of peripheral homeostasis as well as in the protection against
There is substantial evidence suggesting that lymphopenia induced immune
activation may result in autoimmunity, multiorgan immunopathology, as well
as rejection of solid organ transplants. Therefore, understanding the mechanisms
regulating T cell proliferation in lymphopenic conditions has fundamental
biological importance. Our study aims at defining the mechanisms by which
T cell proliferation/differentiation processes are induced and regulated.
How T cells are induced to proliferate without exogenous cognate Ag stimulation?
Why it doesn't occur under non-lymphopenic conditions? We have recently reported
that different subsets of APCs are involved in proliferation of T cell subsets;
namely, naïve and memory CD4 T cell proliferation is completely dependent
on interaction with MHC II molecules exclusively expressed on CD11c+ DCs.
On the other hand, naïve CD8 T cell proliferation still occurs in the
absence of MHC I. Surprisingly, CD8 T cells are capable of interacting with
MHC II molecules when MHC I is absent. For details, see Do et al. PNAS (2009).
We currently examine cellular mechanism that regulates proliferation in vivo.
We are also interested in understanding the contribution of apoptosis of T
cells during homeostatic regulation.
Recently, we became interested in gd T cell subsets that are specialized
in producing IL-17 under non-inflammatory conditions. We identified that these
IL-17+ gd T cells are primarily generated within the thymus during the postnatal
period and that TGF b 1 plays the major role in the generation. However, cellular
mechanism underlying the in vivo generation of IL-17+ gd T cells as well as
their immunologic roles as 'innate IL-17-producers' remain poorly understood.
We are actively pursuing this issue.
Another project that we recently initiated is to examine T cell homeostasis
within nonlymphoid tissues, the CNS during acute and persistent virus infection.
Our lab teamed with Drs. Steve Stohlman and Conni Bergmann (Neuroscience Dept,
CCF), and investigate cellular mechanisms of T cell retention within the CNS
during the JHMV infection. More specifically, we will determine whether viral
Ag presentation induces CD8 T cell retention in the CNS during persistent
infection. Moreover, we will test how CD4 T cells contribute to the survival
and the retention of CD8 T cells in the CNS during persistent infection.
Last project that we investigate is to examine in vivo roles of basophils.
Basophils have recently been studied by many investigators, and their roles
as immune effectors as well as modulators continue to increase. We are particularly
interested in mechanism that mobilizes circulating basophils into the lymphoid
tissues. This will be an interesting topic because it is believed that basophils
which that enter the LN promote the development of Th2 immune responses in
vivo. However, we recently reported that it is not always the case; i.e.,
basophils may be dispensable for Th2 immunity under certain circumstances.
We are in process of dissecting the processes of in vivo migration of circulating
basophils and their participation during Th2-related immune responses.
Jeong-Su Do, Ph.D., Postdoctoral fellow
Sohee Kim, Technician
Hwang, Mi-hyun, Postdoctoral Fellow
Anabelle Visperas, Graduate student
Graham LeGros, Ph.D., Malaghan Medical Research Institute, New Zealand
Pamela Fink, Ph.D., University of Washington
John Letterio, M.D., Case Western Reserve University
Marc Hellerstein, M.D. Ph.D., University of California , Berkeley
Angel Lopez, Ph.D., Centre for Cancer Biology, South Australia
Phares, T. W., S. A. Stohlman, M. Hwang, B. Min, D. R. Hinton, and C. C. Bergmann. (2012). CD4 T cells promote CD8 T cell immunity at the priming and effector site during viral encephalitis. J. Virol. AOP.
Do, J., G. Foucras, A. F. Schenk, M. Shaw, G. Nunez, W. E. Paul, and B. Min. (2012). Both exogenous commensal and endogenous self antigens stimulate T cell proliferation under lymphopenic conditions. Cell. Immunol. 272:117-123.
Min, B. M. A. Brown, and G. Le Gros. (2012). Understanding the roles of basophils: breaking dawn. Immunology AOP.
Do, J., A. Visperas, K. Oh, S. A. Stohlman, and B. Min. (2012). Memory CD4 T cells induce selective expression of IL-27 in CD8+ DC and regulate homeostatic naïve T cell proliferation. J. Immunol. 188:230-237.
Do, J., A. Visperas, R. L. O’brien, and B. Min. (2012). CD4 T cells enhance the generation of IL-17+ γδ T cells. Immunol. Cell. Biol. AOP.
Min, B. (2011). Inside Blood. Deleting Mcl-1 in mast cells: getting two birds with one stone. Blood 118:6729-2730.
Bosch, X. F. Lozano, R. Cervera, M. Ramos-Casals, and B. Min. (2011) Basophils, IgE and autoantibody-mediated kidney disease. J. Immunol. 186:3083-6090.
Do, J., A. Visperas, C. Dong, W. Baldwin, and B. Min. (2011). Cutting Edge: Generation of colitogenic Th17 CD4 T cells is enhanced by IL-17+ γδT cells. J. Immunol. 186:4546-4550.
van Panhuys, N., M. Prout, E. Forbes, B. Min, W. E. Paul, and G. Le Gros. (2011). Basophils are the major producers of IL-4 during primary helminth infection. J. Immunol. 186:2719-2728.
Min, B. (2010). Commentary. Mice that conditionally lack basophils: at last! J. Clin. Invest. 120: 2648-2651.
Min, B. (2010). Basophils induce Th2 immunity: is this final answer? Virulence 1:399-401.
Forbes, E., N. van Panhuys, B. Min, and G. Le Gros. (2010). Differential requirements for IL-4/STAT6 signalling in CD4 T cell fate determination and Th2 immune effector responses. Immunol. Cell. Biol. 88: 240-243.
Gulen, M.F, Z. Kang, K. Bulek, C. Z. Altuntas, M.J. McGeachy, J. Do, H. Xiao, B. Min, V.K. Tuohy, D.J. Cua, and X. Li. (2010). SIGIRR, a negative regulator of IL-1R-TLR suppresses Th17 expansion through IL-1-induced mTOR-mediated cell proliferation. Immunity 32: 54-66.
Kim, S., M. Prout, H. Ramshaw, A. F. Lopez, G. Le Gros, and B. Min. (2010). Cutting Edge: Basophils are transiently recruited to the draining lymph node during helminth infection via IL-3 but infection-induced Th2 immunity develops without basophil LN recruitment or IL-3. J. Immunol. 184: 1143-1147.
Do, J., P.J. Fink, L. Li, R. Spolski, J. Robinson, W. J. Leonard, J. J. Letterio, and B. Min. (2010). Cutting Edge: Spontaneous development of IL-17-producing γδ T cells in the thymus occurs via a TGF1-dependent mechanism. J. Immunol. 184: 1675-1679.
Bulek, K., S. Swaidani, J. Qin, Y. Lu, F. Gulen, B. Min, R. A. Kastelein, M. Aronica, M. Kosz-Vnenchak, and X. Li. (2009). The essential role of SIGIRR in regulation of Th2 immune response. J. Immunol. 182: 2601-2609.
Do, J. and B. Min. (2009). IL-15 produced and trans-presented by DCs underlies homeostatic competition between CD8 and γδ T cells in vivo. Blood 113: 6361-6371.
Kim, S., T. Shen, and B. Min. (2009). Basophils can directly present or cross-present Ag to CD8 lymphocytes and alter CD8 T cell differentiation into IL-10-producing phenotypes. J. Immunol. 183: 3033-3039.
Do, J. and B. Min. (2009). Differential requirements of MHC and of DCs for endogenous proliferation of different T-cell subsets in vivo. Proc. Natl. Acad. Sci. USA 106: 20394-20398.
T. Shen, S. Kim, L. Wang, C. Lantz, J. F. Urban Jr, G. Le Gros, B. Min. (2008). Parasite infection induced basophil production requires T cell production of IL-3 but IL-3 is dispensable for in vivo basophil survival. Int. Immunol. 20: 1201-1209.
Wang, L., N. van Panhuys, J. Hu-Li, S. Kim, G. Le Gros, and B. Min. (2008). Blimp-1 induced by IL-4 plays a critical role in suppressing IL-2 production in activated CD4 T cells. J. Immunol. 181: 5249-5256.
Sharma, P., R. Chakraborty, L. Wang, B. Min, M. L. Tremblay, T. Kawahara, J. D. Lambeth, and S. J. Haque. (2008). Redox regulation of interleukin-4 signaling. Immunity 29: 551-564.
Lantz, C.S., B. Min, M. Tsai, G. Dranoff, and S. J. Galli. (2008). IL-3 is required for the increase in blood basophils during nematode infection in mice, but not for basophil IgE-dependent intra-cellular IL-4 production. Lab. Invest. 88: 1134-1142.
Min, B. (2008). Basophils: what they ‘can do’ and what they ‘actually do’. Nat. Immunol. 9: 1333-1339.
Min, B. and W. E. Paul. (2008). Basophils and type 2 immunity. Curr. Opin Hematol. 15: 59-63.
Min, B. and W. E. Paul. (2008). News & Views. Basophils: in the spotlight at last. Nat. Immunol. 9: 223-225.
Oh, K., T. Shen, G. Le Gros, and B. Min. (2007). Induction of Th2 immunity by murine basophils reveals a novel immunoregulatory role of basophils. Blood 109: 2921-2927.
Do, J., G. Foucras, A. F. Schenk, M. Shaw, G. Nunez, W. E. Paul, and
B. Min. (2011). Both exogenous commensal and endogenous self antigens
stimulate T cell proliferation under lymphopenic conditions. Cell.
Immunol. In Press.
Min, B. (2011). Inside Blood. Deleting Mcl-1 in mast cells: getting
two birds with one stone. Blood In Press.
Min, B. M. A. Brown, and G. Le Gros. (2011). Understanding the roles
of basophils: breaking dawn. Immunology In Press.
Do, J., A. Visperas, K. Oh, S. A. Stohlman, and B. Min. (2011). Memory
CD4 T cells induce selective expression of IL-27 in CD8+ DC and regulate
homeostatic naïve T cell proliferation. J. Immunol. In Press
Bosch, X. F. Lozano, R. Cervera, M. Ramos-Casals, and B.
Min. (2011) Basophils, IgE and autoantibody-mediated kidney disease.
J. Immunol. In Press.
Do, J., A. Visperas, R. L. O’brien, and B. Min. (2011). CD4 T cells enhance the generation of IL-17+ gd T cells. Immunol. Cell. Biol. In Press.