Murine polyclonal T-lymphocyte activation induced by phytohemmagglutinin; differential lymphokine requirements of two unusual activation pathways defined by resistance to blockade by barium and by cyclosporin A.
We have recently demonstrated that polyclonal T-cell activation induced by PHA defines an activation pathway which is resistant to blockade by barium (Ba2+) ions. Other modes of T-cell activation, including ConA-induced responses, are completely blocked by Ba2+, which seems to affect an early Ca2+-dependent step of T-cell activation, as determined by kinetic and competition experiments. In the present study, we have analysed the lymphokine requirements of Ba2+-resistant pathway of PHA-induced T-cell activation by means of functional blocking experiments with monoclonal antibodies (mAbs) directed against mouse IL-2 (mAb S4B6) and against mouse IL-4 (mAb 11B11). We found that Ba2+-resistant T-cell activation can be blocked by either S4B6 or 11B11. Thus, both IL-2 and IL-4 participate in Ba2+-resistant T-cell growth induced by PHA. In addition, we found that cyclosporin A (CsA) completely blocks T-cell activation induced by either ConA or by PHA plus Ba2+, but not T-cell activation induced by PHA in the absence of Ba2+, which is reduced by less than 50% in most experiments. This CsA-resistant proliferative component of the PHA response is, thus, distinct from the Ba2+-resistant response, and is carried out by proliferating T-cells. Although mAbs S4B6 and 11B11 are potent blockers of ConA-induced responses, they failed to block CsA-resistant T-cell growth induced by PHA. At the doses of CsA employed, no IL-2 and/or IL-4 activity could be detected in the supernatants of CsA-treated, PHA-stimulated T-cell cultures. The data indicate that this CsA-resistant pathway is both IL-2 and IL-4-independent. The lymphokine involved in this T-cell activation pathway remains to be identified.
Peçanha
L M
LM
Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Brazil.
Dos Reis
G A
GA
D000818:Animals; D001464:Barium / Q000494:pharmacology*; D003115:Colony-Stimulating Factors / Q000502:physiology; D003208:Concanavalin A / Q000494:pharmacology; D003524:Cyclosporins / Q000494:pharmacology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000502:physiology; D007376:Interleukin-2 / Q000502:physiology; D015847:Interleukin-4; D007378:Interleukins / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008222:Lymphokines / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010835:Phytohemagglutinins / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects*
D003115:Colony-Stimulating Factors; D003524:Cyclosporins; D006133:Growth Substances; D007376:Interleukin-2; D007378:Interleukins; D008222:Lymphokines; D010835:Phytohemagglutinins; D003208:Concanavalin A; D015847:Interleukin-4; D001464:Barium; D016178:Granulocyte-Macrophage Colony-Stimulating Factor