Complement activation during OKT3 treatment: A possible explanation for respiratory side effects

Complement activation during OKT3 treatment: A possible explanation for respiratory side effects. Respiratory side effects that sometimes occur during treatment with anti-CD3 MAb OKT3 might result from pulmonary sequestration of activated neutrophils. Therefore, we studied complement activation in relation to activation and pulmonary sequestration of neutrophils during antirejection treatment with OKT3. In each of nine patients studied, plasma C3a-desarg and C4b/c levels increased compared with pretreatment values already in the first sample taken 15 minutes after the first dose of OKT3 (P < 0.05), with peak values at 15 and 30 minutes, respectively. Levels of neutrophil degranulation product elastase (complexed to α1-antitrypsin) also increased already at 15 minutes after the first dose of OKT3 (P < 0.05), which is before elevated levels of the cytokines TNFα, IL-6 or IL-8 were detectable. In contrast, upon subsequent OKT3 administrations or in the control group treated with methylprednisolone, neither complement activation, cytokine release nor neutrophil degranulation occurred. In five studied patients treated with OKT3, pulmonary sequestration of radiolabeled granulocytes was observed from 3 until 15 minutes after the first dose of OKT3, together with peripheral blood granulocytopenia, which lasted at least 30 minutes. In conclusion, we demonstrate a simultaneous activation of complement and pulmonary sequestration of activated granulocytes immediately following the first dose of OKT3. These phenomena may be involved in the development of respiratory side effects complicating this therapy

A bright, high rotation-measure FRB that skewers the M33 halo

We report the detection of a bright fast radio burst, FRB\,191108, with Apertif on the Westerbork Synthesis Radio Telescope (WSRT). The interferometer allows us to localise the FRB to a narrow 5\arcsec\times7\arcmin ellipse by employing both multibeam information within the Apertif phased-array feed (PAF) beam pattern, and across different tied-array beams. The resulting sight line passes close to Local Group galaxy M33, with an impact parameter of only 18\,kpc with respect to the core. It also traverses the much larger circumgalactic medium of M31, the Andromeda Galaxy. We find that the shared plasma of the Local Group galaxies could contribute $\sim$10\% of its dispersion measure of 588\,pc\,cm$^{-3}$. FRB\,191108 has a Faraday rotation measure of +474\,$\pm\,3$\,rad\,m$^{-2}$, which is too large to be explained by either the Milky Way or the intergalactic medium. Based on the more moderate RMs of other extragalactic sources that traverse the halo of M33, we conclude that the dense magnetised plasma resides in the host galaxy. The FRB exhibits frequency structure on two scales, one that is consistent with quenched Galactic scintillation and broader spectral structure with $\Delta\nu\approx40$\,MHz. If the latter is due to scattering in the shared M33/M31 CGM, our results constrain the Local Group plasma environment. We found no accompanying persistent radio sources in the Apertif imaging survey data

Development of virus-specific CD4(+) T cells during primary cytomegalovirus infection

Although virus-specific CD4(+) T cells have been characterized extensively in latently infected individuals, it is unclear how these protective T-cell responses develop during primary virus infection in humans. Here, we analyzed the kinetics and characteristics of cytomegalovirus-specific (CMV-specific) CD4(+) T cells in the course of primary CMV infection in kidney transplant recipients. Our data reveal that, as the first sign of specific immunity, circulating CMV-specific CD4(+) T cells become detectable with a median of 7 days after first appearance of CMV-DNA in peripheral blood. These cells produce the T helper 1 type (Th1) cytokines IFNγ and TNFα, but not the T helper 2 type (Th2) cytokine IL4. In primary CMV infection, the vast majority of these circulating virus-specific T cells have features of recently activated naive T cells in that they coexpress CD45RA and CD45R0 and appear to be in the cell cycle. In contrast, in people who have recovered from CMV infection earlier in life, virus-specific T cells do not cycle and express surface markers characteristic of memory T cells. After the initial rise, circulating virus-specific CD4(+) T cells decline rapidly. During this phase, a strong rise in IgM and IgG anti-CMV antibody titers occurs, concomitant with the reduction of CMV-DNA in the circulation