Biology

Dr. Vineeta Bal
National Institute of Immunology, New Delhi

CD4 T cells form one of the major effector arm of the adaptive immune system. They help in containment of infections and production of good quality antibodies by B cells. We have been pursuing work to understand the biology and function of mouse and human CD4 T cells and work related to  three different aspects with obvious logical interlinkage will be discussed. We have shown that naïve CD4 T cells from aged mice respond poorly and die easily following activation, unlike those from the young mice. This can simple-mindedly be attributed to ‘ageing’. Curiously, we observed that a subset of naïve CD4 T cells from young mice behaves similar to cells from aged mice. That subset of naïve CD4 T cells which expresses low levels of CD4 (CD4lo cells) in a unimodally distributed population shows the similarity with cells from the aged mice. Post-activation, CD4lo cells from young mice showed a cytokine secretion pattern which was different from CD4hi cells, thus further confirming diversity in the unimodally distributed population. In another series of experiments we discovered that there is diversity in the cells which show unimodal distribution of transcription factors T-bet and GATA-3. The current dogma describes transcription factor T-bet as the master regulator of Th1 (T helper 1) response and GATA-3 as master regulator of Th2 (T helper 2) response. T-bet and GATA-3 also negatively regulate each other’s expression. We observe that GATA-3 expressing cells also produce interferon-gamma, a classical Th1 cytokine, in addition to producing Th2 cytokines. Same is true for T-bet, thus questioning the dogma. We also discover that early expression of transcription factor does not necessarily lead to the functional commitment of CD4 T cells as has been assumed. Thus, we observe that within 6 hours of activating CD4 T cells at 40c temperature, instead of the usual 37c, GATA-3 expression comes up significantly. However, this does not lead to an early Th2 commitment of CD4 T cells, unless hyperthermic condition extends to beyond 24, possibly 48, hours. Since infections and inflammations lead to increase in body temperature in the range of 38-40c, we are interested in figuring out how CD4 T cells which get activated during hyperthermia respond and behave. Not just neurons but T cells and dendritic cells have TRPV1 receptors (also known as the capsaicin receptor and the vanilloid receptor 1) which sense temperature changes in the body and our data provide some insights about signalling through TRPV receptors and T cell differentiation.