REGULATORY INTERACTIONS BETWEEN CD45RB(HIGH) AND CD45RB(LOW) CD4(-CELLS ARE IMPORTANT FOR THE BALANCE BETWEEN PROTECTIVE AND PATHOGENIC CELL-MEDIATED-IMMUNITY() T)

BALB/c mice infected with the intracellular protozoan Leishmania major mount a T helper cell 2 (Th2) response that fails to control growth o f the parasite and results in the development of visceral leishmaniasi s. Separation of CD4(+) T cells into CD45RB(high) and CD45RB(low) subs ets showed that the L. major-specific Th2 cells were contained within the CD45RB(low) population as these cells produced high levels of anti gen-specific interleukin 4 (IL-4) in vitro and transferred a nonhealin g response to L. major-infected C.B-17 scid mice. In contrast, the CD4 5RB(high)CD4(+) population contained L. major-reactive cells that prod uced interferon gamma (IFN-gamma) in vitro and transferred a healing T h1 response to L. major-infected C.B-17 scid mice. Transfer of the Th1 response by the CD45RB(high) population was inhibited by the CD45RB(l ow) population by a mechanism that was dependent on IL-4. These data i ndicate that L. major-specific Th1 cells do develop in BALB/c mice, bu t their functional expression is actively inhibited by production of I L-4 by Th2 cells. In this response, the suppressed Th1 cells can be ph enotypically distinguished from the suppressive Th2 cells by the level of expression of CD45RB. Although the CD45RB(high) population mediate d a protective response to L. major, C.B-17 scid mice restored with th is population developed a severe inflammatory response in the colon th at was independent of L. major infection, and was prevented by cotrans fer of the CD45RB(low) population. The colitis appeared to be due to a dysregulated Th1 response as anti-IFN-gamma, but not anti-IL-4, preve nted it. Taken together, the data show that the CD4(+) T cell populati on identified by high level expression of the CD45RB antigen contains cells that mediate both protective and pathogenic Th1 responses and th at the reciprocal CD45RB(low) population can suppress both of these re sponses. Whether suppression of cell-mediated immunity is beneficial o r not depends on the nature of the stimulus, being deleterious during L. major infection but crucial for control of potentially pathogenic i nflammatory responses developing in the gut.